title: Kinoid of human tumor necrosis factor-alpha for rheumatoid arthritis.
abstract: BACKGROUND
  Anti-TNF-α drugs have dramatically changed treatment of rheumatoid arthritis (RA) in terms of both clinical control and articular damage prevention. Despite this, they hold some important drawbacks, such as frequent therapeutic failures and high costs. Anti-TNF-α active immunization, with a therapeutic vaccine against TNF-α, is a promising alternative anti-TNF-α targeting strategy, potentially devoid of treatment limitations of some of current anti-TNF blocking agents.
  
  
  METHODS
  This review covers the preclinical proof-of-concept of anti-TNF-α vaccination with the kinoid of human TNF-α (TNFK) and analyzes the body of evidence forming the rationale for the application of this strategy in RA and other TNF-α-dependent diseases. We describe the theoretical bases of anti-TNF-α active immunization and of experimental data supporting the applicability of TNFK to human disease in terms of both safety and efficacy.
  
  
  CONCLUSIONS
  Based on preclinical efficacy and safety data supporting its feasibility in a Phase I - II trial in Crohn's disease, anti-TNF-α vaccination with TNFK has entered the phase of clinical development and promises to be a valuable anti-TNF-α targeting strategy in human disease. The focus is made in the first clinical trial in RA (Phase II) on the efficacy in active RA patients having developed antibodies against anti-TNF mAbs.
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Avicenne, Rheumatology Department, 125 rue de Stalingrad, 93000 Bobigny, France.
authors.forename: Luca
authors.initials: L
authors.lastname: Semerano
authors.forename: Eric
authors.initials: E
authors.lastname: Assier
authors.forename: Laure
authors.initials: L
authors.lastname: Delavallée
authors.forename: Marie-Christophe
authors.initials: MC
authors.lastname: Boissier
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014612:Vaccines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D014612:Vaccines